ES2483722T3 - Análogos quiméricos de somatostatina-dopamina - Google Patents
Análogos quiméricos de somatostatina-dopamina Download PDFInfo
- Publication number
- ES2483722T3 ES2483722T3 ES08171319.0T ES08171319T ES2483722T3 ES 2483722 T3 ES2483722 T3 ES 2483722T3 ES 08171319 T ES08171319 T ES 08171319T ES 2483722 T3 ES2483722 T3 ES 2483722T3
- Authority
- ES
- Spain
- Prior art keywords
- compound
- alkyl
- somatostatin
- formula
- allyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
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- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 22
- 150000003839 salts Chemical class 0.000 claims abstract description 22
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 18
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims abstract description 18
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 18
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 13
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 12
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 4
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims abstract description 4
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| BR112017015510A2 (pt) | 2015-01-20 | 2018-01-30 | Xoc Pharmaceuticals Inc | composto de fórmula estrutural (i), método de tratamento e/ou prevenção, método de agonização do receptor d2 em um indivíduo, método de antagonização do receptor d3 em um indivíduo, método de agonização do receptor 5-ht1d em um indivíduo, método de agonização do receptor 5-ht1a em um indivíduo, método de agonização seletiva do receptor 5-ht1d em vez do receptor 5-ht1b em um indivíduo, método de agonização seletiva do re-ceptor 5-ht2c em vez do receptor 5-ht2a ou 5-ht2b em um indivíduo, método de agonização do receptor 5-ht2c em um indivíduo, método de fornecimento de atividade antagonista funcional no receptor 5-ht2b ou receptor 5-ht7, e, método de fornecimento de atividade antagonista funcional nos receptores adrenérgicos em um indivíduo |
| CA3064274A1 (en) | 2017-06-01 | 2018-12-06 | Xoc Pharmaceuticals, Inc. | Ergoline derivatives for use in medicine |
| WO2023225043A1 (en) * | 2022-05-18 | 2023-11-23 | Kuleon Llc | Tricyclic and tetracyclic serotonin receptor modulators and methods of making and using the same |
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| FR98F (de) | 1961-05-29 | |||
| AT258479B (de) * | 1961-05-29 | 1967-11-27 | Farmaceutici Italia | Verfahren zur Herstellung von neuen Verbindungen aus der Klasse des D-6-Methyl- (und -1,6-Dimethyl)-8-amino-methyl-ergolins I |
| US3966941A (en) * | 1970-09-23 | 1976-06-29 | Spofa United Pharmaceutical Works | Composition for preventing lactation or pregnancy in mammals and the method for using the same |
| US3901894A (en) | 1974-06-06 | 1975-08-26 | Lilly Co Eli | 8-thiomethylergolines |
| US4291022A (en) | 1975-03-11 | 1981-09-22 | Sandoz Ltd. | Organic compounds |
| HU172479B (hu) * | 1976-03-09 | 1978-09-28 | Gyogyszerkutato Intezet | Sposob poluchenija novykh soedinenij s ehrgolenovymi i |
| US4133782A (en) | 1976-06-07 | 1979-01-09 | The Salk Institute For Biological Studies | Somatostatin analogs with dissociated biological activities |
| US4190575A (en) | 1977-12-27 | 1980-02-26 | American Home Products Corporation | Polypeptides related to somatostatin |
| EP0000053B1 (de) | 1977-06-08 | 1981-05-27 | Merck & Co. Inc. | Somatostatin-ähnliche Verbindungen, Verfahren zu ihrer Herstellung und pharmazeutische Zusammensetzungen, die sie enthalten |
| US4357259A (en) | 1977-08-01 | 1982-11-02 | Northwestern University | Method of incorporating water-soluble heat-sensitive therapeutic agents in albumin microspheres |
| US4211693A (en) | 1977-09-20 | 1980-07-08 | The Salk Institute For Biological Studies | Peptides with para-substituted phenylalanine |
| LU78191A1 (de) | 1977-09-28 | 1979-05-25 | Ciba Geigy Ag | Verfahren zur herstellung von neuen cyclopeptiden |
| US4166182A (en) | 1978-02-08 | 1979-08-28 | Eli Lilly And Company | 6-n-propyl-8-methoxymethyl or methylmercaptomethylergolines and related compounds |
| CA1107273A (en) | 1978-05-19 | 1981-08-18 | Chester A. Meyers | Somatostatin analogs having a substituted tryptophyl residue in position eight |
| JPS5819669B2 (ja) | 1978-10-28 | 1983-04-19 | 白井松新薬株式会社 | 新規生理活性ペプチド化合物及びその製造法 |
| DD140044A1 (de) * | 1978-11-08 | 1980-02-06 | Guenter Losse | Verfahren zur herstellung von lysergyl-enkephalin-derivaten |
| US4215039A (en) | 1979-02-15 | 1980-07-29 | American Home Products Corporation | Somatostatin analogues |
| US4190648A (en) | 1979-03-13 | 1980-02-26 | Merck & Co., Inc. | Peptides having somatostatin activity |
| US4316890A (en) | 1979-03-16 | 1982-02-23 | Ciba-Geigy Corporation | Peptides and processes for the manufacture thereof |
| US4209426A (en) | 1979-05-29 | 1980-06-24 | American Home Products Corporation | Polypeptides related to somatostatin |
| US4328214A (en) | 1979-07-04 | 1982-05-04 | Ciba-Geigy Corporation | Cyclopeptides and pharmaceutical preparations thereof and also processes for their manufacture |
| US4235886A (en) | 1979-10-31 | 1980-11-25 | Merck & Co., Inc. | Cyclic hexapeptide somatostatin analogs |
| US4310518A (en) | 1979-10-31 | 1982-01-12 | Merck & Co., Inc. | Cyclic hexapeptide somatostatin analogs |
| ATE2512T1 (de) | 1979-11-27 | 1983-03-15 | Sandoz Ag | Polypeptide, verfahren zu ihrer herstellung, pharmazeutische zusammensetzungen, die diese polypeptide enthalten, und ihre verwendung. |
| US4369179A (en) | 1979-12-14 | 1983-01-18 | Ciba-Geigy Corporation | Acylpeptides |
| US4358439A (en) | 1979-12-21 | 1982-11-09 | Ciba-Geigy Corporation | Cyclooctapeptides |
| US4282143A (en) | 1980-06-13 | 1981-08-04 | American Home Products Corporation | Octapeptides lowering growth hormone |
| US4526892A (en) * | 1981-03-03 | 1985-07-02 | Farmitalia Carlo Erba, S.P.A. | Dimethylaminoalkyl-3-(ergoline-8'βcarbonyl)-ureas |
| DK81082A (da) | 1981-03-06 | 1982-09-07 | Sandoz Ag | Fremgangsmaade til fremstilling af polypeptider |
| US4360516A (en) | 1981-04-13 | 1982-11-23 | Merck & Co., Inc. | Modified D-retro cyclic hexapeptide somatostatin analogs |
| GB2103603B (en) * | 1981-08-11 | 1985-04-11 | Erba Farmitalia | Ergoline derivatives |
| GB2112382B (en) | 1981-11-06 | 1985-03-06 | Erba Farmitalia | Ergoline derivatives |
| EP0083305B1 (de) | 1981-12-24 | 1985-07-10 | Ciba-Geigy Ag | Cyclische Octapeptide und pharmazeutische Präparate davon, sowie Verfahren zur Herstellung derselben und ihre Anwendung |
| FR2522655B1 (fr) | 1982-03-05 | 1987-03-06 | Sanofi Sa | Analogues de la somatostatine possedant une liaison du type hydrazide et medicaments en contenant |
| PH21123A (en) | 1983-04-28 | 1987-07-27 | Erba Farmitalia | Ergoline derivatives |
| US4486415A (en) | 1983-08-15 | 1984-12-04 | Merck & Co., Inc. | Cyclic hexapeptide somatostatin analogs |
| US4485101A (en) | 1983-10-11 | 1984-11-27 | Administrators Of The Tulane Educational Fund | Peptides |
| US4522813A (en) | 1983-10-27 | 1985-06-11 | Merck & Co., Inc. | Cyclic hexapeptide somatostatin analogs |
| US4684620A (en) | 1984-09-04 | 1987-08-04 | Gibson-Stephens Neuropharmaceuticals, Inc. | Cyclic polypeptides having mu-receptor specificity |
| HUT42101A (en) | 1985-01-07 | 1987-06-29 | Sandoz Ag | Process for preparing stomatostatine derivatives and pharmaceutical compositions containing such compounds |
| US4725577A (en) | 1985-04-25 | 1988-02-16 | Administrators Of The Tulane Educational Fund | Biologically active lysine containing octapeptides |
| US4650787A (en) | 1985-04-25 | 1987-03-17 | Schally Andrew Victor | Biologically active octapeptides |
| US4585755A (en) | 1985-04-29 | 1986-04-29 | Merck & Co., Inc. | Cyclic and bridged cyclic somatostatin analogs useful as local anti-inflammatory agents |
| US4904642A (en) | 1985-09-12 | 1990-02-27 | The Administrators Of The Tulane Educational Fund | Therapeutic somatostatin analogs |
| US4853371A (en) | 1986-06-17 | 1989-08-01 | The Administrators Of The Tulane Educational Fund | Therapeutic somatostatin analogs |
| HU206890B (en) | 1986-10-13 | 1993-01-28 | Sandoz Ag | Process for producing sugar-modified somatostatin peptide derivatives and pharmaceutical compositions containing them as active components |
| US4871717A (en) | 1987-01-07 | 1989-10-03 | Administrators Of The Tulane Educational Fund | Peptides |
| DE3845000C2 (de) * | 1987-07-10 | 1998-11-19 | Novartis Ag | Anwendung von Octreotid zur Behandlung von Brustkrebs |
| EP0329295A1 (de) | 1988-02-01 | 1989-08-23 | The Upjohn Company | Renin inhibierende Peptide mit polaren Endgruppen |
| GB8813339D0 (en) * | 1988-06-06 | 1988-07-13 | Sandoz Ltd | Improvements in/relating to organic compounds |
| DK375789A (da) | 1988-08-18 | 1990-02-19 | Syntex Inc | Peptidderivater |
| CA2012115C (en) | 1989-03-15 | 2001-07-03 | Biomeasure, Inc. | Iodinated somatostatins |
| JP2882679B2 (ja) | 1989-04-26 | 1999-04-12 | ジ・アドミニストレーターズ・オブ・ザ・ツーレイン・エデュケイショナル・ファンド | 線状ソマトスタチン類似体 |
| US5621133A (en) * | 1989-05-31 | 1997-04-15 | Deninno; Michael P. | Dopamine agonists |
| HU203549B (en) | 1989-06-27 | 1991-08-28 | Richter Gedeon Vegyeszet | New stereoselektive hydrogenating process for producing dihydro-lisergol |
| HUT59166A (en) | 1989-12-08 | 1992-04-28 | Univ Tulane | Process for producing octqpeptide somatostatine analogues with treonine at the 6 position and pharmaceutical compositions containing them |
| US5411966A (en) * | 1990-01-15 | 1995-05-02 | Schering Aktiengesellschaft | 2, 13-disubstituted ergolines, their production and use in pharmaceutical agents |
| DK0464178T3 (da) | 1990-01-25 | 1996-01-02 | Pharmacia Spa | Fremgangsmåde til fremstilling af ergolinderivater |
| US5043341A (en) * | 1990-04-11 | 1991-08-27 | Eli Lilly And Company | N-(2-hydroxycyclopentyl)-1-isopropyl-6-methylergoline-8-carboxamides |
| IT1240643B (it) | 1990-05-11 | 1993-12-17 | Mediolanum Farmaceutici Spa | Peptidi biologicamente attivi contenenti in catena 2-alchiltriptofano |
| EP0538395A4 (en) * | 1990-07-10 | 1993-06-16 | Synaptic Pharmaceutical Corporation | Nucleic acid sequences encoding a human dopamine d 1? receptor |
| HU207104B (en) | 1991-01-25 | 1993-03-01 | Biosignal Kutato Fejlesztoe Kf | Process for producing new somatostatin analogs inhibiting tumour growth and pharmaceutical compositions comprising such compounds |
| WO1994004752A1 (en) | 1992-08-20 | 1994-03-03 | Industrial Progress, Inc. | Acid-to-alkaline papermaking process |
| ATE204278T1 (de) * | 1992-12-24 | 2001-09-15 | Pharmacia & Upjohn Spa | Serotoninergische ergolin derivate |
| FR2699923B1 (fr) | 1992-12-28 | 1995-03-17 | Great Lakes Chemical France | Copolymères d'esters gras insaturés, leur utilisation comme additif de viscosité et huile lubrifiante contenant lesdits copolymères. |
| AU692435B2 (en) * | 1993-01-21 | 1998-06-11 | United States Of America, As Represented By The Secretary Of Agriculture, The | Vaccines and methods for preventing and treating fescue toxicosis in herbivo res |
| MY147327A (en) | 1995-06-29 | 2012-11-30 | Novartis Ag | Somatostatin peptides |
| AU2582197A (en) * | 1996-03-15 | 1997-10-01 | Start Technology Partnership | Methods and compositions for diagnosis and treatment of pathological conditions related to abnormal dopamine receptor expression |
| US5925618A (en) * | 1997-03-06 | 1999-07-20 | American Cyanamid Company | Peptides useful as somatostatin antagonists |
| GB9711043D0 (en) * | 1997-05-29 | 1997-07-23 | Ciba Geigy Ag | Organic compounds |
| DE19832191A1 (de) | 1998-07-17 | 2000-01-27 | Knoell Hans Forschung Ev | Neuartige Ergolinamin-Derivate und ihre Verwendung |
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